CN110721602B - Vitamin B6Hyperbranched polymer modified polymer membrane and preparation method and application thereof - Google Patents

Vitamin B6Hyperbranched polymer modified polymer membrane and preparation method and application thereof Download PDF

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CN110721602B
CN110721602B CN201910955114.4A CN201910955114A CN110721602B CN 110721602 B CN110721602 B CN 110721602B CN 201910955114 A CN201910955114 A CN 201910955114A CN 110721602 B CN110721602 B CN 110721602B
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membrane
polymer film
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CN110721602A (en
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何洋
江鹏
陈莉
赵义平
邓泽鹏
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Tianjin Polytechnic University
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D71/00—Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
    • B01D71/06—Organic material
    • B01D71/66—Polymers having sulfur in the main chain, with or without nitrogen, oxygen or carbon only
    • B01D71/68—Polysulfones; Polyethersulfones
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/24—Dialysis ; Membrane extraction
    • B01D61/243—Dialysis
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D67/00—Processes specially adapted for manufacturing semi-permeable membranes for separation processes or apparatus
    • B01D67/0081—After-treatment of organic or inorganic membranes
    • B01D67/0093—Chemical modification
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D69/00—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
    • B01D69/02—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor characterised by their properties

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Abstract

The invention provides vitamin B6A hyperbranched polymer modified polymer film, a preparation method and an application thereof relate to the field of modified polymer films. The method comprises (1) preparing vitamin B6A solution; (2) immersing the polymer film in the vitamin B6In the solution, reacting to obtain vitamin B6A modified polymer film; (3) preparing an amino-terminal hyperbranched polyglycidyl ether solution; (4) mixing the above vitamin B6And immersing the modified polymer film in the amino-terminal hyperbranched polyglycidyl ether solution for reaction to obtain the product. The polymer membranes of the invention are capable of passing vitamin B in hemodialysis applications6Intervene in Hcy metabolism, effectively reduce the Hcy level in human bodies, and have good protein pollution resistance and blood compatibility by the construction of the hyperbranched polyglycidyl ether polymer layer.

Description

Vitamin B6Hyperbranched polymer modified polymer membrane and preparation method and application thereof
Technical Field
The invention relates to the field of modified polymer films, in particular to vitamin B6Hyperbranched polymer modified polymer membrane and preparation method and application thereof.
Background
The treatment method used clinically at present mainly comprises a blood purification technology, and mainly comprises leading blood out of the body and removing harmful substances in the blood by using a purification device.
Hemodialysis is one of the most widely used blood purification techniques, and can effectively remove low-molecular toxins such as urea, creatinine and the like, but the level of homocysteine (Hcy) in blood of a patient with renal failure who carries out hemodialysis for a long time is 2-4 times higher than that of a normal person, and the symptom is called hyperhomocysteinemia (HHcy). High Hcy level can not only cause oxidative stress reaction and damage vascular endothelial cells, but also high concentration Hcy can promote the oxidation of low density lipoprotein, stimulate the proliferation of vascular smooth muscle cells and cause atherosclerosis, and HHcy can also cause cardiovascular diseases such as cerebral apoplexy, thrombosis and the like.
Hcy is an intermediate product of methionine metabolism circulation in vivo, the content of Hcy is closely related to whether the metabolic process is normal or not, the methionine metabolism is mainly divided into two ways of re-methylation and transsulfuration, wherein the re-methylation requires vitamin B12Folic acid as the essential coenzyme for metabolic reaction, vitamin B as the key coenzyme in the transsulfuration pathway6Thus, vitamin B6Vitamin B12And folic acid deficiency causes HHcy, while the kidney is mainly the transsulfuration pathway, so vitamin B is used for patients with renal failure who undergo hemodialysis for a long time6Plays a key role in reducing the Hcy level in the body of a patient.
Currently, in clinical treatment, parenteral supplementary drug therapy is usually required, and the operation is relatively complex. The development of a hemodialysis membrane capable of specifically removing Hcy, and the realization of controlling the Hcy level in the plasma of a hemodialysis patient during dialysis are one of the development directions with great clinical significance at present.
Disclosure of Invention
The invention provides a membrane which has high-efficiency specific removal capacity for homocysteine (Hcy) and can achieve the aim of high-efficiency protein adsorption resistance by loading a medicament on the surface of a hemodialysis membrane, thereby realizing hemodialysis and reducing the high Hcy content in a patient body.
The invention provides a vitamin B6A preparation method of a hyperbranched polymer modified polymer membrane comprises the following steps:
(1) adding vitamin B into trihydroxymethyl aminomethane buffer solution6And metal salt to obtain vitamin B6A solution;
(2) immersing the polymer film in the vitamin B6In the solution, reacting to obtain vitamin B6A modified polymer film;
(3) adding amino-terminal hyperbranched polyglycidyl ether and metal salt into the trihydroxymethyl aminomethane buffer solution to obtain amino-terminal hyperbranched polyglycidyl ether solution;
(4) mixing the above vitamin B6Immersing the modified polymer film in the amino-terminal hyperbranched polyglycidyl ether solution for reaction to obtain vitamin B6Hyperbranched polymer-modified polymer membranes.
Further, the step (2) also comprises the steps of pretreating the polymer film; the pretreatment specifically comprises the following steps: the polymer film is respectively treated by soaking and cold plasma.
Further, in the step (2), the soaking treatment is respectively soaking by absolute ethyl alcohol and deionized water; the cold plasma treatment time is 5-20min, the power is 100W-300W, and the used atmosphere comprises oxygen, nitrogen and air.
Further, in the step (2), the polymer membrane is one of a polyvinylidene fluoride membrane, a polytetrafluoroethylene membrane, a polysulfone membrane, a polyether sulfone membrane, a polyacrylonitrile membrane, a polyurethane membrane or a regenerated cellulose membrane;
in the step (2), the reaction is a constant temperature oscillation reaction, the reaction temperature is 25-45 ℃, and the oscillation time is 2-24 h.
Further, in the step (1), vitamin B6The final concentration of the solution is 0.5-5 g/L;
in the step (3), the final concentration of the amino-terminal hyperbranched polyglycidyl ether solution is 0.1-10 g/L.
Further, in the step (1) and the step (3), the final concentration of the tris buffer solution is 0.5-5g/L, and the pH is 7.0-11.0;
in the step (1) and the step (3), the final concentration of the metal salt is 5-50 g/L;
in the step (1) and the step (3), the metal salt is one or a mixture of more than two of sodium chloride, magnesium chloride, copper chloride, ferric chloride and aluminum chloride.
Further, the step (2) also comprises post-treatment; the method specifically comprises the following steps: mixing vitamin B6Modifying the polymer film, washing and drying to constant weight;
the step (4) also comprises post-treatment; the method specifically comprises the following steps: mixing vitamin B6And washing and drying the hyperbranched polymer modified polymer film.
Further, the drying is carried out in a vacuum oven or a freeze dryer for 6-12 h.
The invention also provides vitamin B prepared by the method6Hyperbranched polymer-modified polymer membranes.
The invention also provides the vitamin B6Application of hyperbranched polymer modified polymer membrane in hemodialysis.
The invention has the following beneficial effects:
(1) the invention provides a vitamin B6Hyperbranched polymer modified polymer film, preparation method and application thereof, based on vitamin B6The vitamin B has the characteristic of extremely high potential in the aspect of material surface functionalization by containing various functional groups, and the vitamin B is constructed on the surface of a polymer film6Coating, and further reacting with Schiff base in vitamin B6The hyperbranched polyglycidyl ether is grafted on the coating to construct a surface protein adsorption resistant polymer layer, so that the hemodialysis membrane has good blood compatibility and protein pollution resistance, and can intervene in Hcy metabolism in dialysis to reduce the Hcy level in vivo.
(2) The experiment of the protein adsorption resistance of the modified polymer film proves that the adhesion between the surface of the polymer film and protein is obviously reduced along with the construction of the hyperbranched polyglycidyl ether polymerization layer on the surface of the film, and the minimum adhesion can be reduced to 5.98nN from 55.17nN, so that the modified polymer film has excellent protein adhesion resistance along with the construction of the hyperbranched polyglycidyl ether polymerization layer on the surface of the film. The Hcy removing capacity test of the modified polymer film can obtain that the removing rate of the modified polymer film gradually increases along with the increase of the treatment time, and the final removing rate can reach more than 80 percent, so that the Hcy concentration level approaches to the normal level of a human body.
Drawings
The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate an embodiment of the invention and, together with the description, serve to explain the invention and not to limit the invention.
FIG. 1 is a schematic flow chart illustrating the preparation of a modified polymer membrane according to an embodiment of the present invention.
Fig. 2 is a graph of contact angle test results for a pure polymer film and a modified polymer film in an example of the present invention.
FIG. 3 is a graph showing the results of the interaction force between the surface of the pure polymer film and the surface of the modified polymer film with protein in the example of the present invention.
FIG. 4 is a graph showing the results of measurement of homocysteine-removing ability of pure polymer films and modified polymer films in the examples of the present invention.
Detailed Description
It should be noted that the embodiments and features of the embodiments may be combined with each other without conflict.
The embodiment of the invention provides vitamin B6A preparation method of a hyperbranched polymer modified polymer membrane comprises the following steps:
(1) preparing vitamin B6Solution: adding vitamin B to Tris buffer6And metal salt to obtain vitamin B6A solution;
(2) vitamin B6Modified polymer film: immersing the polymer film in the vitamin B6In the solution, reacting to obtain vitamin B6A modified polymer film;
(3) preparing amino-terminal hyperbranched polyglycidyl ether (NH)2-HPG) solution: adding NH to Tris buffer2-HPG and metal salts to obtain NH2-a HPG solution;
(4) mixing the above vitamin B6The modified polymer film was immersed in the above-mentioned NH2Reacting in HPG solution to obtain vitamin B6Hyperbranched polymer-modified polymer membranes.
FIG. 1 is a flow chart illustrating the preparation of a modified polymer membrane according to an embodiment of the present invention. Embodiments of the invention are based on vitamin B6Contains multiple functional groups, and vitamin B is constructed on the surface of the polymer film6Coating, then reacting with Schiff base in vitamin B6Hyperbranched polyglycidyl ether is grafted on the coating to construct a surface protein adsorption resistant polymer layer, so that the hemodialysis membrane has good blood compatibility and protein pollution resistance, and key coenzyme vitamin B required by Hcy metabolism in the body of a hemodialysis patient is supplemented6So that the Hcy metabolism is smoothly carried out and the Hcy content in vivo is reduced.
Vitamin B6Consists of one pyridine ring, one aldehyde group, phosphoric acid and hydroxyl, vitamin B6The phosphate group of (a) enables the formation of a P-O-metal coordination bond, and the pyridine structure is one of the most important heterocyclic compounds in natural products. In addition, the material also contains various chemical groups (phosphate, benzene, phenol, hydroxyl, aldehyde group and the like), can be used as a chemical component part anchored on the surface and is an ideal material for surface chemical application.
In contrast to other surface-modifying substances, firstly, vitamin B6Can be obtained in large quantities without time-consuming organic synthesis; secondly, the inherent biological activity function is easily introduced through the surface of the immobilized vitamin, and a platform is provided for the secondary functionalization of the material surface. However, vitamin B6The aldehyde group can react with primary amine of protein and polypeptide to generate Schiff-base, which causes protein adsorption and accumulation in the process of blood contact of biomedical materials and causes dangerous situations such as thrombus and the like.
In the present example, HPG was further grafted to vitamin B6Coating the surface of the substrate with vitamin B6The aldehyde group reacts with proteins in blood, etc. Firstly, HPG can form a plurality of self-assembly forms and is an ideal substrate of the three-dimensional comb-type graft copolymer; secondly, compared with a homopolymer and a blending system consisting of the homopolymer, the HPG can form a more stable spatial structure on the surface due to the unique three-dimensional dendritic structure, has great steric hindrance effect and can reject contact adsorption of protein; thirdly, the HPG contains a large number of ether bonds inside, can form stronger hydrogen bonds with hydrogen atoms, has polyhydroxy terminal functional groups and the like, has better water solubility, oil solubility and biocompatibility compared with other three-dimensional structure high polymers, and is used for modifying the hemodialysis membrane for resisting protein pollutionAnd (4) excellent selection.
In one embodiment of the present invention, in step (1), vitamin B6The final concentration of the solution is 0.5-5 g/L. In particular vitamin B6Vitamin B in solution6To the final concentration of (c).
In an embodiment of the present invention, the step (2) further includes pretreating the polymer film; the method specifically comprises the following steps: the polymer film is respectively treated by soaking and cold plasma.
In an embodiment of the present invention, in the step (2), the soaking treatment is performed by soaking in absolute ethyl alcohol and soaking in deionized water, respectively.
In one embodiment of the invention, the cold plasma treatment time is 5-20min, the power is 100W-300W, and the used atmosphere comprises oxygen, nitrogen and air. The polymer film treated by the plasma in the embodiment of the invention can accelerate the reaction speed.
The method specifically comprises the following steps: immersing the polymer film in absolute ethyl alcohol for 0.5-1h, then immersing in deionized water for 0.5-1h, and repeating the steps for 2-4 times; after treatment, the polymer film was placed in deionized water for use.
In one embodiment of the present invention, vitamin B6Modification by dip coating in solution and application in vitamin B6The modified coating further depends on Schiff base to generate reaction grafted hyperbranched polyglycidyl ether, which has the characteristics of simple operation and mild reaction, and has no limit to the appearance, size, membrane material and the like of the polymer membrane. Preferably, the polymer membrane may be one of a polyvinylidene fluoride membrane, a polytetrafluoroethylene membrane, a polysulfone membrane, a polyethersulfone membrane, a polyacrylonitrile membrane, a polyurethane membrane, or a regenerated cellulose membrane.
In one embodiment of the invention, in the step (2), the reaction is a constant temperature oscillation reaction, the reaction temperature is 25-45 ℃, and the oscillation time is 2-24 h.
In one embodiment of the present invention, step (2) further comprises vitamin B6Post-treating the modified polymer film; the method specifically comprises the following steps: mixing vitamin B6And (3) modifying the polymer film, washing and drying to constant weight.
The layer-by-layer modified polymer film provided by the embodiment of the invention has the advantages of simple preparation method and green colorAnd high efficiency. Vitamin B6The preparation of the coating utilizes the modification of a matrix polymer film and vitamin B6Can be used as modifier to generate nonspecific deposition on the surfaces of different materials, and increase vitamin B6The binding action site between the coating and the polymer film of the matrix effectively enhances the binding force between the coating and the polymer matrix, and has high retention rate in the application process.
In one embodiment of the present invention, in step (3), NH2The final concentration of the HPG solution is between 0.1 and 10 g/L.
In the examples of the present invention, NH2The preparation of-HPG is a conventional process known to the person skilled in the art. Specifically, may be NH2-the method of preparation of HPG comprises: n, N-2 benzyl hydroxymethyl aminomethane (Bn2Tris) is taken as an initiator, glycidyl ether is taken as a monomer to carry out ring-opening multi-branched polymerization reaction, and the benzyl protection group is removed by synthesizing the hyperbranched polyglycidyl ether with benzyl protection under the conditions of palladium-carbon catalysis and hydrogen reduction, and the selective conversion of amino is carried out to obtain the hyperbranched polyglycidyl ether with amino terminal.
In one embodiment of the present invention, in the step (1) and the step (3), the Tris buffer solution has a final concentration of 0.5 to 5g/L and a pH of 7.0 to 11.0.
In one embodiment of the invention, in the step (1) and the step (3), the final concentration of the metal salt is 5-50 g/L.
In one embodiment of the present invention, in the step (1) and the step (3), the metal salt is one or a mixture of two or more of sodium chloride, magnesium chloride, copper chloride, ferric chloride and aluminum chloride.
In an embodiment of the present invention, the step (4) further includes, post-processing; the method specifically comprises the following steps: mixing vitamin B6And washing and drying the hyperbranched polymer modified polymer film.
Specifically, the drying is carried out in a vacuum oven or a freeze dryer for 6-12 h.
In the examples of the present invention, vitamin B6And the hyperbranched polyglycidyl ether and the membrane are combined with a reaction medium which is water, so that the damage of the performance of the membrane body and the environmental pollution caused by an organic solvent are avoided.
In one embodiment of the present invention, vitamin B6、NH2The ratio of the HPG-modified polymer film to the polymer film may be appropriate. Preferably, vitamin B6：NH2-an HPG: the final mass ratio of the polymer film may be (0.01-0.1): (0.002-0.2): 1.
the embodiment of the invention also provides vitamin B prepared by the method6Hyperbranched polymer-modified polymer membranes.
An embodiment of the present invention further provides vitamin B6Application of hyperbranched polymer modified polymer membrane in hemodialysis. The hemodialysis membrane has good blood compatibility and protein pollution resistance, and can supplement key coenzyme vitamin B required by Hcy metabolism in a hemodialysis patient6Thereby leading the Hcy metabolism to be smoothly carried out and reducing the Hcy content in vivo.
The present invention will be described in detail below with reference to the accompanying drawings.
Example 1Vitamin B6Preparation of hyperbranched polymer layer-by-layer modified polymer film
1) Pretreatment of a polymer film: the polymer film is immersed in a beaker containing absolute ethyl alcohol for soaking for 0.5h, and then soaked in deionized water for 0.5h, and the steps are repeated for 3 times. And after the treatment, placing the polymer film in deionized water, taking out and drying after the organic solvent is completely removed, and performing oxygen plasma treatment on the polymer film for 10min under an oxygen atmosphere, wherein the use power is 150W. Wherein the polymer membrane is a polyether sulfone membrane PES.
2) Preparing vitamin B6Solution: tris buffer solution was prepared at a concentration of 1g/L, pH of 8.5. Mixing 2.5g vitamin B635.06g of sodium chloride is added into 1L of Tris buffer solution, and the mixture is stirred for 5min to be fully dissolved to obtain uniform vitamin B6And (3) solution.
3) Preparing amino-terminal hyperbranched polyglycidyl ether (NH)2-HbPG) solution: adding 13g/L, 35g/L and 40g/L of NH2Adding HbPG into Tris buffer solutions with concentration of 1g/L, pH of 8.5, and stirring to obtain NH with final concentrations of 1.3g/L, 3.5g/L and 4.0g/L2-HbPG solution.
4) Vitamin B6Preparation of hyperbranched polymer layer-by-layer modified polymer film: immersing the pretreated polymer film in a solution containing vitamin B6Placing the solution beaker in a thermostatic waterbath oscillator with the temperature of 25 ℃, the rotating speed of 30rpm and the reaction time (namely the dip-coating time) of 4h, taking out the polymer film from the beaker, repeatedly rinsing the polymer film for 10 minutes by deionized water, and removing the vitamin B with the surface bonded with infirm6The vitamin B is completely dipped and coated6Is placed in NH2Reacting in-HbPG solution for 12h, washing and drying to obtain vitamin B6The hyperbranched polymer is used for modifying the polymer film layer by layer.
5) Vitamin B6Post-treatment of the hyperbranched polymer layer-by-layer modified polymer film: freeze-drying the modified membrane in a freeze-dryer for 12h, and taking out the membrane after complete drying.
Example 2Vitamin B6Preparation of hyperbranched polymer layer-by-layer modified polymer film
1) Pretreatment of a polymer film: the polymer film is immersed in a beaker containing absolute ethyl alcohol for soaking for 0.5h, and then soaked in deionized water for 0.5h, and the steps are repeated for 3 times. And after the treatment, placing the polymer film in deionized water, taking out and drying after the organic solvent is completely removed, and carrying out plasma treatment on the polymer film for 10min under the nitrogen atmosphere, wherein the use power is 150W. Wherein the polymer membrane is a polyether sulfone membrane.
(2) Formulating vitamin B6Solution: tris buffer solution with the concentration of 1g/L is prepared, and HCl or NaOH aqueous solution with the concentration of 0.1mol/L is used for adjusting the pH value to 7.0. Mixing 2.5g vitamin B635.06g sodium chloride is added into 1LTris buffer solution, and stirred for 5min to dissolve completely to obtain uniform vitamin B6Solutions of
(3) Preparing amino-terminal hyperbranched polyglycidyl ether (NH)2-HbPG) solution: adding 13g/L, 35g/L and 40g/L of NH2Adding HbPG into Tris buffer solutions with concentration of 1g/L, pH of 8.5, and stirring to obtain NH with final concentrations of 1.3g/L, 3.5g/L and 4.0g/L2HbPG solution
(4) Vitamin preparationB6Preparation of hyperbranched polymer layer-by-layer modified polymer film: immersing the pretreated polymer film in a solution containing vitamin B6Placing the solution beaker in a thermostatic water bath oscillator with the temperature of 25 ℃, the rotating speed of 30rpm and the reaction time (namely the dip-coating time) of 10h, taking out the polymer film from the beaker, repeatedly rinsing the polymer film for 10 minutes by deionized water, and removing the vitamin B with the surface bonded with infirm6The vitamin B is completely dipped and coated6Is placed in NH2Reacting in-HbPG solution for 12h, washing and drying to obtain vitamin B6The hyperbranched polymer is used for modifying the polymer film layer by layer.
(5) Vitamin B6Post-treatment of the hyperbranched polymer layer-by-layer modified polymer film: freeze-drying the modified membrane in a freeze-dryer for 12h, and taking out the membrane after complete drying.
Example 3Vitamin B6Preparation of hyperbranched polymer layer-by-layer modified polymer film
(1) Pretreatment of a polymer film: the polymer film is immersed in a beaker containing absolute ethyl alcohol for soaking for 0.5h, and then soaked in deionized water for 0.5h, and the steps are repeated for 3 times. And after the treatment, placing the polymer film in deionized water, taking out and drying after the organic solvent is completely removed, and carrying out plasma treatment on the polymer film for 10min under the air atmosphere, wherein the use power is 250W. Wherein the polymer membrane is a polyether sulfone membrane.
(2) Formulating vitamin B6Solution: tris buffer solution with the concentration of 1g/L is prepared, and HCl or NaOH aqueous solution with the concentration of 0.1mol/L is used for adjusting the pH value to 7.0. Mixing 2.5g vitamin B635.06g sodium chloride is added into 1LTris buffer solution, and stirred for 5min to dissolve completely to obtain uniform vitamin B6And (3) solution.
(3) Preparing amino-terminal hyperbranched polyglycidyl ether (NH)2-HbPG) solution: adding 13g/L, 35g/L and 40g/L of NH2Adding HbPG into Tris buffer solutions with concentration of 1g/L, pH of 8.5, and stirring to obtain NH with final concentrations of 1.3g/L, 3.5g/L and 4.0g/L2-HbPG solution.
(4) Vitamin B6Hyperbranched polymer layer-by-layer modified polymerPreparation of compound film: immersing the pretreated polymer film in a solution containing vitamin B6Placing the solution beaker in a thermostatic water bath oscillator with the temperature of 25 ℃, the rotating speed of 30rpm and the reaction time (namely the dip-coating time) of 10h, taking out the polymer film from the beaker, repeatedly rinsing the polymer film for 10 minutes by deionized water, and removing the vitamin B with the surface bonded with infirm6The vitamin B is completely dipped and coated6Is placed in NH2Reacting in-HbPG solution for 12h, washing and drying to obtain vitamin B6The hyperbranched polymer is used for modifying the polymer film layer by layer.
(5) Vitamin B6Post-treatment of the hyperbranched polymer layer-by-layer modified polymer film: freeze-drying the modified membrane in a freeze-dryer for 12h, and taking out the membrane after complete drying.
The modified films obtained in the examples of the present invention were subjected to the following performance tests.
Blank control group: mpristineRepresents: a pure PES membrane;
experimental groups: a modified polymeric film prepared according to the preparation method of example 1, wherein vitamin B will only be dip coated6The polymer film product of (A) is noted as MPLPDip-coating vitamin B6And further reacting with 1.3g/L, 3.5g/L and 4.0g/L NH2The polymer film products of the HbPG reaction are respectively denoted as MHPG1.99、MHPG3.07、MHPG3.96。
Test example 1Hydrophilic Property measurement of modified Polymer Membrane
Water contact angle test: the measurement of water contact angle is based on the contact angle that a test liquid, i.e. water, forms with a solid surface at three-phase equilibrium at a solid/liquid/gas or solid/liquid interface. And (3) performing a contact angle test on the membrane sample by using a contact angle tester (DSA 100) to characterize the hydrophilicity and hydrophobicity of the membrane surface.
The experimental steps are as follows: quantitative pure water (5 mu L) is dripped on the surface of a film sample of 1cm multiplied by 4cm through a micro syringe on a contact angle tester, the contact process of the liquid and the film surface is recorded in real time, and the included angle between the tangent of a water drop-gas interface at the intersection point of three phases and the boundary line of the water drop-film surface is measured by analysis software, wherein the angle is the contact angle theta.
When theta is less than 90 degrees, the membrane surface is defined as hydrophilic, a liquid is easy to wet a solid, and the smaller the water contact angle is, the more hydrophilic the membrane surface is, and the hydrophilicity and the hydrophobicity of the membrane are important factors influencing the anti-pollution performance of the membrane.
FIG. 2 is a PES film contact angle test chart before and after modification.
As can be seen from FIG. 2, MpristineIs 92.70 deg., and the membrane surface is hydrophobic. When dip-coated with vitamin B6Then, MPLPThe initial contact angle was brought to 74.64 °, and after further grafting of the hyperbranched polymer layer, there was a more pronounced decrease in the contact angle, compared to Mpristine，MHPG1.99、MHPG3.07、MHPG3.96The contact angles of (a) decrease to 58.4 °, 55.3 ° and 57.7 °, respectively. And M in the subsequent 60spristineThe contact angle of (A) is reduced by only 2.35 DEG, while MPLP、MHPG1.99、MHPG3.07、MHPG3.96The contact angles are respectively reduced by 16.58 degrees, 19.5 degrees, 23.2 degrees and 21.3 degrees, which indicates that the vitamin B6And the hyperbranched polyglycidyl ether form a hydrophilic layer on the surface of the membrane and in the pore channel, so that the wettability of the membrane to water is enhanced.
Test example 2Protein adsorption resistance test of modified polymer film
Interaction force test between protein contaminants and membrane surface: the AFM force curve test is utilized to detect the interaction force between the surface of the polymer membrane and different proteins (bovine serum albumin, human serum albumin and fibrin), and the adhesion force generated by the contact between the membrane surface and the proteins is compared, so that the protein adsorption resistance of the modified membrane and the unmodified membrane is most intuitively characterized.
The experimental steps are as follows: testing using Si adapted for contact mode3N4And (3) performing oxygen plasma treatment on the probe, then placing the probe in a 10 mmol/L3-aminopropyltriethoxysilane (KH550) solution to react at room temperature for 2h to obtain an amino-terminated AFM probe, taking out the AFM probe, placing the AFM probe in a 50% glutaraldehyde aqueous solution to react for 30min, then reacting the AFM probe with protein in a phosphate buffer (pH 7.4), and finally obtaining the protein-modified AFM probe tips, the interaction force between the tip near the retracted polymer surface and the immobilized protein on the tip surface was measured by AFM (Dimension Icon, Bruker, Germany) force curve testing, and the adhesion force generated by the protein leaving the surface after contact with the membrane surface was determined.
M in FIG. 3(A), FIG. 3(B) and FIG. 3(C)pristine，MPLP、MHPG1.99、MHPG3.07、MHPG3.96Schematic diagram of the adhesion force between the protein and bovine serum albumin, human serum albumin and fibrinogen respectively.
As can be seen from FIG. 3, in contrast to MpristineAnd MPLPGrafting of NH2After HbPG, the adhesion between the polymer membrane and bovine serum albumin, human serum albumin and fibrinogen is obviously reduced, which indicates that the construction success of the hyperbranched polymer layer endows the membrane surface with excellent protein adsorption resistance.
Test example 3Determination of Hcy scavenging Capacity of modified Polymer films
The experimental conditions are as follows: preparing Hcy solution with concentration of 150 mu mol/L to simulate blood of a patient with hyperhomocysteinemia, placing unmodified and modified polymer membrane products in the solution, oscillating for 1-4h, taking out the simulated solution as sample solution for testing under the treatment time of 0.25h, 0.5h, 1.0h, 1.5h, 2.0h, 2.5h, 3.0h, 3.5h and 4.0h respectively, adding pyridoxal 5' -phosphate into the sample for derivatization reaction, reacting at 45 ℃ for 15min, and then placing at room temperature for stabilization for 2 h.
The sample liquid was quantitatively detected by High Performance Liquid Chromatography (HPLC) equipped with an ultraviolet detector. HPLC using a detection wavelength of 340nm, using a gradient elution procedure: 0-2.5min, 80-50% B: 20-50% of A; 2.5-3.5min, 50-80% B: 50-20% of A; 3.5-5min, 80% B: 20% A, wherein the mobile phase A is 0.05mol/L phosphate buffer solution with pH 3, the mobile phase B is chromatographically pure methanol, and the elution rate is 1.0 mL/min.
As is clear from fig. 4(a), the peak area of Hcy gradually decreased with the increase of the treatment time, and the peak area after 4 hours had a very significant decrease and was almost gentle compared to the initial Hcy peak area. Indicating that the modified membrane has a very significant effect of reducing the level of Hcy concentration.
As can be seen from FIG. 4(B), the clearance of Hcy is obviously improved after the first hour compared with that of the pure film, and gradually increased along with the increase of the treatment time, and finally the clearance can reach more than 80%, and the original concentration of 150 mu mol/L Hcy (the highest Hcy concentration level defined in medicine) can be reduced to 20 mu mol/L (close to the normal human body level), and the result shows that the vitamin B on the surface of the film6The existence of the coating can effectively remove excessive Hcy in blood and reduce the occurrence of risk diseases.
The present invention is not limited to the above preferred embodiments, and any modifications, equivalent substitutions, improvements, etc. within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims (9)

1. Vitamin B6The preparation method of the hyperbranched polymer modified polymer membrane is characterized by comprising the following steps:
(1) adding vitamin B into trihydroxymethyl aminomethane buffer solution6And metal salt to obtain vitamin B6A solution;
(2) immersing the polymer film in the vitamin B6In the solution, reacting to obtain vitamin B6A modified polymer film;
(3) adding amino-terminal hyperbranched polyglycidyl ether and metal salt into the trihydroxymethyl aminomethane buffer solution to obtain amino-terminal hyperbranched polyglycidyl ether solution;
(4) mixing the above vitamin B6Immersing the modified polymer film in the amino-terminal hyperbranched polyglycidyl ether solution for reaction to obtain vitamin B6Hyperbranched polymer-modified polymer membranes.
2. The method of claim 1,
the step (2) further comprises pretreating the polymer film; the pretreatment specifically comprises the following steps: the polymer film is respectively treated by soaking and cold plasma.
3. The method of claim 2,
in the step (2), the soaking treatment is respectively soaking by absolute ethyl alcohol and deionized water; the cold plasma treatment time is 5-20min, the power is 100W-300W, and the used atmosphere comprises oxygen, nitrogen and air.
4. The method of claim 1,
in the step (2), the polymer membrane is one of a polyvinylidene fluoride membrane, a polytetrafluoroethylene membrane, a polysulfone membrane, a polyether sulfone membrane, a polyacrylonitrile membrane, a polyurethane membrane or a regenerated cellulose membrane;
in the step (2), the reaction is a constant-temperature oscillation reaction, the reaction temperature is 25-45 ℃, and the oscillation time is 2-24 h.
5. The method of claim 1,
in the step (1), the vitamin B6The final concentration of the solution is 0.5-5 g/L;
in the step (3), the final concentration of the amino-terminal hyperbranched polyglycidyl ether solution is 0.1-10 g/L.
6. The method of claim 1,
in the step (1) and the step (3), the final concentration of the tris buffer solution is 0.5-5g/L, and the pH value is 7.0-11.0;
in the step (1) and the step (3), the final concentration of the metal salt is 5-50 g/L;
in the step (1) and the step (3), the metal salt is one or a mixture of more than two of sodium chloride, magnesium chloride, copper chloride, ferric chloride and aluminum chloride.
7. The method of claim 1,
the step (2) also comprises post-treatment; utensil for cleaning buttockThe body is as follows: mixing vitamin B6Modifying the polymer film, washing and drying to constant weight;
the step (4) further comprises post-treatment; the method specifically comprises the following steps: mixing vitamin B6And washing and drying the hyperbranched polymer modified polymer film.
8. The method of claim 7,
the drying is carried out in a vacuum oven or a freeze dryer, and the drying time is 6-12 h.
9. Vitamin B prepared by the process of any one of claims 1 to 86Hyperbranched polymer-modified polymer membranes.
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